Document Type
Article
Publication Title
Journal of Biological Chemistry
Publication Date
6-2-1995
Volume
270
Issue
22
Disciplines
Biology | Life Sciences
Abstract
Activation of the cell surface receptors for tumor necrosis factor (TNF) is effected by the aggregation of cytoplasmic domains that occurs when the extracellular domains of two or three receptors bind to trimeric TNFα or TNFβ. The structure of the type I TNF receptor extracellular domain (sTNF- R1), crystallized in the absence of TNF, has now been determined at 2.25-Å resolution. The receptor itself is an elongated molecule comprising four disulfide-rich domains in a nearly linear array. Contrary to expectations, the unliganded domains are found to associate into dimers of two distinct types, in which monomers are related by local two-fold axes of symmetry. In one case, the receptors are antiparallel to each other and associate through an interface that overlaps the TNF binding site. If intact receptors were capable of such an association, their cytoplasmic domains would be separated by over 100 Å. This interaction could inhibit signaling in the absence of TNF. Parallel dimers are also observed in which the dimer interface is well separated from the TNF binding site. Associations among TNF-bound parallel dimers could cause receptor clustering. Both dimers bury substantial areas of protein surface and are formed by polar and non-polar interactions.
DOI
https://doi.org/10.1074/jbc.270.22.13303
Rights
© 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Naismith, James H.; Devine, Tracey Q.; Brandhuber, Barbara J.; and Sprang, Stephen R., "Crystallographic evidence for dimerization of unliganded tumor necrosis factor receptor" (1995). Biological Sciences Faculty Publications. 545.
https://scholarworks.umt.edu/biosci_pubs/545